Imperial College London

Dr Chris Dunsby

Faculty of Natural SciencesDepartment of Physics

Reader in Biomedical Optics
 
 
 
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Contact

 

+44 (0)20 7594 7755christopher.dunsby Website

 
 
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Location

 

622Blackett LaboratorySouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Fang:2020:10.1021/acsptsci.0c00022,
author = {Fang, Z and Chen, S and Pickford, P and Broichhagen, J and Hodson, DJ and Corrêa, IR and Kumar, S and Görlitz, F and Dunsby, C and French, PMW and Rutter, GA and Tan, T and Bloom, SR and Tomas, A and Jones, B},
doi = {10.1021/acsptsci.0c00022},
journal = {ACS Pharmacology & Translational Science},
pages = {345--360},
title = {The influence of peptide context on signaling and trafficking of glucagon-like peptide-1 receptor biased agonists},
url = {http://dx.doi.org/10.1021/acsptsci.0c00022},
volume = {3},
year = {2020}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Signal bias and membrane trafficking have recently emerged as important considerations in the therapeutic targeting of the glucagon-like peptide-1 receptor (GLP-1R) in type 2 diabetes and obesity. In the present study, we have evaluated a peptide series with varying sequence homology between native GLP-1 and exendin-4, the archetypal ligands on which approved GLP-1R agonists are based. We find notable differences in agonist-mediated cyclic AMP signaling, recruitment of β-arrestins, endocytosis, and recycling, dependent both on the introduction of a His → Phe switch at position 1 and the specific midpeptide helical regions and C-termini of the two agonists. These observations were linked to insulin secretion in a beta cell model and provide insights into how ligand factors influence GLP-1R function at the cellular level.
AU - Fang,Z
AU - Chen,S
AU - Pickford,P
AU - Broichhagen,J
AU - Hodson,DJ
AU - Corrêa,IR
AU - Kumar,S
AU - Görlitz,F
AU - Dunsby,C
AU - French,PMW
AU - Rutter,GA
AU - Tan,T
AU - Bloom,SR
AU - Tomas,A
AU - Jones,B
DO - 10.1021/acsptsci.0c00022
EP - 360
PY - 2020///
SN - 2575-9108
SP - 345
TI - The influence of peptide context on signaling and trafficking of glucagon-like peptide-1 receptor biased agonists
T2 - ACS Pharmacology & Translational Science
UR - http://dx.doi.org/10.1021/acsptsci.0c00022
UR - https://pubs.acs.org/doi/10.1021/acsptsci.0c00022
UR - http://hdl.handle.net/10044/1/77863
VL - 3
ER -